Chloramphenicol, 2.2-dichloro-N [2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]acetamide is a broad based antibiotic that has long been known to inhibit protein synthesis in both gram positive and gram negative bacteria. Presently in disfavor in a number of developed countries for use in humans and food animals, due to its association in with aplastic anemia in humans, chloramphenicol continues to be employed, for treating companion animals worldwide, and livestock in developing countries. A close structural analogue, thiamphenicol, D-threo-2,2-dichloro-N-[β-hydroxy-α-(hydroxymethyl)-p-methylsulfonyl)phenethyl]acetamide, see structures below, has a similar broad spectrum of activity, but has never been associated with aplastic anemia. Chloramphenicol and thiamphenicol have the chemical formulas

Thiamphenicol is currently used worldwide to treat animals with bacterial infections, and is currently used in the treatment of humans in China. Also known in the art are analogs of these compounds having substituents other than nitro and methylsulfonyl, for example compounds in which the 4-substituent on the phenyl ring is selected from

As stated above, chloramphenicol and thiamphenicol have broad spectrum antibiotic activity against many gram-negative and gram-positive bacteria, including utility in the prevention and treatment of bacterial infections due to susceptible pathogens in birds, reptiles, fish, shellfish and mammals. Examples of susceptible organisms include: Mannheimia haemolytica, Pasteurella multocida, Haemophilus somnus, also known as Histophilus somni, Fusobacterium necrophorum, Bacterioides melaninogenicus, Actinobacillus pleuropneumoniae, Streptococcus suis, Salmonella cholerasuis, Mycoplasma spp., Escherichia coli; Edwardsiella ictaluri, Aeromonas salmonicida, Enterobacter, Klebsiella, Staphylococcus, Enterococcus, Bordetella, Proteus, Shigella, K. pneumoniae, E. cloacae, and S. typhus. 
Given the need for economical, single-dose treatment in the veterinary setting, there remains a need for new formulations of chloramphenicol and/or thiamphenicol at high concentrations. In addition, there is also a need for forms of chloramphenicol and thiamphenicol that are capable of maintaining effective plasma antibiotic levels for prolonged periods of time, in order to achieve improved economies in administration, e.g., to more readily provide single dose treatment, particularly in a veterinary setting. In addition there is a need for similar forms of chloramphenicol and thiamphenicol analogs.
One of the important applications is a treatment of bacterial infections by dosing the drug in drinking water given to animals. Such means of administration provides effective treatment of bacterial infection since chloramphenicol and thiamphenicol are reasonably well absorbed from the intestine ad achieves necessary antibacterial systemic levels. However, as mentioned above, the aqueous solubility of these compounds is quite limited; consequently their solubilization in water is slow. Achieving the desired concentrations in drinking water requires preparation of pre-dissolved chloramphenicol or thiamphenicol in the form of a concentrate in a water-miscible organic solvent. Additionally, a water-soluble prodrug of either compound or of an analog of either that was easily dissolved directly in the drinking water for animals would be quite desirable.
Known in the prior art are water-soluble prodrugs of these two antibiotics produced by esterification of the relatively easily accessible primary alcohol group. Glycinates of these compounds have been extensively investigated, for example. Some examples of such esters are disclosed in U.S. Pat. Nos. 3,740,411 and 3,770,889 (both of Akiyama et al.). British patent 1,263,116 of Sumitomo Chemical Co., and 3,405,165 and 3,475,470 (both of Rebstock et al.). However, there still remains a need for alternative forms of chloramphenicol or thiamphenicol that have additional beneficial features.
A provisional patent application, U.S. Ser. No. 60/874,864 filed Dec. 13, 2006, drawn to analogous florfenicol prodrugs was filed with the U.S. Patent and Trademark Office on the same day as the provisional application from which the present application claims priority. It also should be noted that the citation of any reference herein should not be construed that such reference is available as “prior art” to the instant Application.